OBJECTIVE: To report the most up-to-date evidence on the effects of tumour necrosis factor (TNF)-alpha inhibition on cartilage with a focus on its clinical relevance. DESIGN: A systematic review was performed by searching PubMed, Embase and Cochrane Library databases. Inclusion criteria were studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results written in English. Relative data were extracted and critically analysed. PRISMA guidelines were applied, and risk of bias was assessed as well as the methodological quality of the included studies. RESULTS: 13 studies were included after applying the inclusion and exclusion criteria. Three were in vitro human studies from osteoarthritis (OA) patients. Ten were animal modal studies including two in vitro studies, and eight in vivo studies. TNF-alpha inhibition in in vitro studies was generally reported beneficial due to the improved osteochondral viability, proliferation and chondrogenesis. In addition, TNF-alpha inhibition was noted to be beneficial in promoting the natural repair of osteochondral lesions and has a chondroprotective effect in in vivo studies. CONCLUSION: Based on current evidence, TNF might have the potential to interfere with the healing process of chondral and osteochondral defects occurring naturally or in low inflammatory environment after a cartilage repair procedure. Therefore, the use of biological agents to inhibit its action in cartilage repair surgery could be beneficial, and this could translate into a promising therapy that improves the outcome of currently available cartilage procedures.